What is the difference between peripheral and central sensitization?

Peripheral sensitization is an increased responsiveness of nociceptor terminals in injured or inflamed tissue, whereas central sensitization is increased responsiveness of nociceptive neurons within the central nervous system, especially the spinal dorsal horn.

Why can light touch become painful?

When central nociceptive neurons are sensitized, they can respond to normally innocuous input, so that a stimulus like light touch is perceived as painful, a phenomenon called allodynia.

Central Sensitization

Central sensitization is an increase in the responsiveness of nociceptive neurons in the central nervous system, so that normal or subthreshold input produces exaggerated pain. It is a form of activity-dependent plasticity, principally in the spinal dorsal horn, and is a central mechanism by which pain hypersensitivity is generated and maintained.

Definition

Central sensitization is an increased responsiveness of nociceptive neurons in the central nervous system to their normal or subthreshold afferent input, producing pain hypersensitivity through activity-dependent changes in synaptic strength and excitability.

Scope

This topic covers the synaptic and circuit mechanisms of central sensitization, its behavioral signatures (allodynia and secondary hyperalgesia), the loss of inhibitory control that contributes to it, and the role of non-neuronal cells. It is a reference treatment of a core pain mechanism, not clinical guidance.

Core questions

What synaptic changes underlie increased central excitability?
How does central sensitization produce allodynia and secondary hyperalgesia?
How does loss of inhibitory control contribute to central sensitization?
What roles do glia and immune signaling play?

Key concepts

Activity-dependent synaptic plasticity
Dorsal horn hyperexcitability
Allodynia
Secondary hyperalgesia
Loss of inhibitory tone (disinhibition)
Glial and immune signaling

Key theories

Activity-dependent central plasticity: Intense or sustained nociceptive input strengthens synaptic transmission and raises the excitability of dorsal-horn neurons, so the central pain system amplifies its output; this plasticity, together with reduced inhibition and glial contributions, generates pain hypersensitivity.

Mechanisms

Central sensitization arises when nociceptive input drives lasting increases in the strength and efficacy of synaptic transmission within the spinal dorsal horn and related central circuits. Sensitized second-order neurons fire more readily and respond to input that would normally be subthreshold or innocuous, which manifests behaviorally as allodynia (pain from normally non-painful stimuli) and as hyperalgesia spreading beyond the site of injury. A reduction in fast synaptic inhibition can disinhibit dorsal-horn circuits and contribute to this amplification. Non-neuronal cells, including microglia and astrocytes, release mediators that further enhance and maintain neuronal sensitization, linking central sensitization to neuroinflammation.

Clinical relevance

Central sensitization is a unifying concept for understanding why pain can become widespread, why gentle stimuli can hurt, and why pain may persist without continuing injury. This entry describes the mechanism for reference and does not provide assessment or treatment recommendations for individuals.

Evidence & guidelines

The account follows mechanistic reviews of central sensitization and spinal pain processing (Latremoliere & Woolf, 2009; Woolf & Salter, 2000; Zeilhofer et al., 2012) and of non-neuronal contributions to pain (Ji et al., 2016).

History

Central sensitization was identified through experiments showing that the excitability of spinal neurons could be increased by nociceptive input rather than being fixed. The concept was progressively refined to encompass synaptic potentiation, loss of inhibition, and glial involvement, and it became a foundational explanation for pain hypersensitivity across many conditions.

Key figures

Clifford Woolf
Alban Latremoliere
Hanns Ulrich Zeilhofer
Ru-Rong Ji

Seminal works

woolf-2000
latremoliere-2009
zeilhofer-2012
ji-2016

Frequently asked questions

What is the difference between peripheral and central sensitization?: Peripheral sensitization is an increased responsiveness of nociceptor terminals in injured or inflamed tissue, whereas central sensitization is increased responsiveness of nociceptive neurons within the central nervous system, especially the spinal dorsal horn.
Why can light touch become painful?: When central nociceptive neurons are sensitized, they can respond to normally innocuous input, so that a stimulus like light touch is perceived as painful, a phenomenon called allodynia.